As discussed in our recently published overview of the study, we enrolled 50,884 US and Puerto Rican women who were between the ages of 35 and 74 and had a sister with breast cancer but did not have breast cancer themselves when they joined the study between 2003 and 2009. At enrollment, data on potential risk factors and current health status were collected using computer assisted telephone interviews and mailed questionnaires. Blood, urine, and environmental samples were collected in a home visit and banked for future use in nested studies of women who develop breast cancer (or other diseases) and a sample of those who don't. More than 3,000 Sister Study participants have reported a diagnosis of invasive or in situ breast cancer. The cohort is tracked annually for changes in vital status and major health outcomes. Detailed follow-up questionnaires on health outcomes, environmental and lifestyle exposures, and special topics are completed every 2-3 years. We retrieve medical records and tumor tissue for those who develop cancer or other conditions of interest. In 2014-15 we repeated the collection of biological and environmental samples from women diagnosed with breast cancer since enrollment and a random sample of the cohort. Of approximately 3,800 participants invited, samples were collected from 2,436 (63%) including 1,229 women who had been diagnosed with breast cancer. These paired repeat samples will allow us to explore changes in biomarkers and exposures over time and in relation to breast cancer diagnosis and treatment. So far, we have published one study that made use of twice-collected biospecimens. Here, we assessed concentrations of 16 trace elements from toenails collected at baseline and in 2014-15, finding that levels generally decreased over time, particularly for cadmium, chromium and lead. In summer 2017 we began contacting participants to obtain comprehensive updates on family history of cancers relevant to breast cancer risk prediction. Currently 84% of participants have responded to this survey. Additionally, beginning in December 2017 we started requesting mammography records from a sample of participants so that we can identify modifiable determinants of breast density and assess whether changes in breast density modify risk (collaborators Parisa Tehranifar and Mary Beth Terry from Columbia University). In the spring of 2018 we began mailing smell test kits to a sample of participants identified for a study of air pollution and olfactory function (collaborator Honglei Chen, Michigan State University). Breast cancer and ovarian cancer cases through 2014 and a random sample of the cohort have been genotyped as part of the multi-study Oncoarray project. Through this project, Sister Study data have been included in several collaborative analyses, including two recent transcriptome-wide association studies and studies of potentially novel loci for overall or estrogen-receptor-negative breast cancer. We also previously generated data on 450,000 CpGs for the non-Hispanic white women in the genotyping sample, with plans to evaluate methylation patterns in relation to risk factors of interest. The first such analysis to be published was an analysis of vitamin D, DNA methylation and breast cancer. Our collaboration with researchers from the Division of Cancer Prevention and Control at the Centers for Disease Control and Prevention to study quality of life in breast cancer survivors continues. A survey of approximately 20,000 Sister Study participants in 2012 focused on the impact of having a sister with breast cancer. A second survey, completed in May 2013, involved women diagnosed with breast cancer and included topics that are of interest to younger women such as body image, work-life balance, and fertility. We previously observed an inverse association between high levels of serum 25-hydroxyvitamin D and breast cancer risk. Following-up on this work, we reported that single nucleotide polymorphisms in vitamin D-related genes may modify vitamin D-breast cancer associations. In a genome-wide association study, we identified two loci associated with serum 25-hydroxyvitamin D levels.